Apixaban for the Treatment of Venous Thromboembolism Associated With Cancer - Caravaggio

Apr 23, 2020
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Presenter/Author:
Giancarlo Agnelli, MD
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Bristol-Myers Squibb–Pfizer Alliance
Date Presented:
03/29/2020
Date Published:
03/29/2020
Date Updated:
04/23/2020
Original Posted Date:
03/29/2020
References

Contribution To Literature:

The Caravaggio trial showed that twice daily apixaban was noninferior at preventing recurrent venous thromboembolism compared with subcutaneous dalteparin.


Description:

The goal of the trial was to evaluate apixaban compared with dalteparin among patients with cancer-associated proximal deep vein thrombosis or pulmonary embolus.

Study Design

  • Randomized
  • Parallel
  • Open label

Cancer patients with proximal deep vein thrombosis or pulmonary embolus were randomized to apixaban (n = 576) versus dalteparin (n = 579).

In the apixaban arm, subjects received 10 mg twice daily for 7 days, then 5 mg twice daily from 7 days until 6 months.

In the dalteparin arm, subjects received 200 IU/kg subcutaneous daily for 7 days, then 150 IU/kg subcutaneous daily from 7 days until 6 months.

  • Total number of enrollees: 1,170
  • Duration of follow-up: 6 months
  • Mean patient age: 67 years
  • Percentage female: 49%

Inclusion criteria:

  • Symptomatic or incidental proximal lower-limb deep vein thrombosis, symptomatic pulmonary embolus, or incidental pulmonary embolus in a segmental or more proximal pulmonary artery
  • Active cancer
  • History of cancer within last 2 years (maximum proportion of patients meeting this inclusion criterium was set at 20%)

Exclusion criteria:

  • Age <18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status III or IV
  • Life expectancy <6 months
  • Therapeutic doses of low molecular weight heparin, fondaparinux, unfractionated heparin, or vitamin K antagonist >72 hours before randomization
  • Indication for anticoagulant treatment other than the index venous thromboembolism
    Concomitant use of strong inhibitors or inducers of both CYP-3A4/P-gp or concomitant P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) or aspirin therapy
  • Active bleeding or a high risk of bleeding
  • Anemia/thrombocytopenia

Principal Findings:

The primary efficacy outcome, recurrent proximal deep vein thrombosis/pulmonary embolism, occurred in 5.6% of the apixaban group compared with 7.9% of the dalteparin group (p for superiority = 0.08, p for noninferiority < 0.001).

The primary safety outcome, bleeding (European Medicines Agency [EMA] definition), occurred in 3.8% of the apixaban group compared with 4.0% of the dalteparin group (p = 0.60).

Secondary outcomes:

  • Recurrent deep vein thrombosis: 2.3% of the apixaban group compared with 2.6% of the dalteparin group
  • Recurrent pulmonary embolism: 3.3% of the apixaban group compared with 5.5% of the dalteparin group
  • Fatal pulmonary embolism: 0.7% of the apixaban group compared with 0.5% of the dalteparin group
  • Major gastrointestinal (GI) bleeding: 1.9% of the apixaban group compared with 1.7% of the dalteparin group

Interpretation:

Among cancer patients with proximal deep vein thrombosis or pulmonary embolus, apixaban was noninferior compared with subcutaneous dalteparin on prevention of recurrent venous thromboembolism. There was no increase in major bleeding or GI bleeding. Among cancer patients, treatment guidelines recommend low molecular weight heparin, edoxaban, or rivaroxaban; however, edoxaban and rivaroxaban have been associated with an increased incidence of GI bleeding. For some cancer patients with proximal deep vein thrombosis or pulmonary embolus, apixaban twice daily therapy would be an appropriate treatment option.

References:

Agnelli G, Becattini C, Meyer G, et al., on behalf of the Caravaggio Investigators. Apixaban for the Treatment of Venous Thromboembolism Associated With Cancer. N Engl J Med 2020;382:1599-607.

Editorial: Lee AY. Anticoagulant Therapy for Venous Thromboembolism in Cancer. N Engl J Med 2020;382:1650-2.

Presented by Dr. Giancarlo Agnelli at the American College of Cardiology Virtual Annual Scientific Session Together With World Congress of Cardiology (ACC 2020/WCC), March 29, 2020.

Clinical Topics: Anticoagulation Management, Cardio-Oncology, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: acc20, ACC Annual Scientific Session, Anticoagulants, Cardiotoxicity, Dalteparin, Heparin, Low-Molecular-Weight, Neoplasms, Pulmonary Embolism, Secondary Prevention, Vascular Diseases, Venous Thromboembolism, Venous Thrombosis


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